The effect of streptozotocin induced diabetes on sperm function: a closer look at AGEs, RAGEs, MAPKs and activation of the apoptotic pathway

Temidayo S Omolaoye; Stefan S Du Plessis

doi:10.1007/s43188-020-00040-7

The effect of streptozotocin induced diabetes on sperm function: a closer look at AGEs, RAGEs, MAPKs and activation of the apoptotic pathway

Toxicol Res. 2020 Apr 24;37(1):35-46. doi: 10.1007/s43188-020-00040-7. eCollection 2021 Jan.

Authors

Temidayo S Omolaoye¹, Stefan S Du Plessis^{1

2}

Affiliations

¹ Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Tygerberg, 7505 South Africa.
² Department of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.

Abstract

This study was designed to (1) investigate the possible mechanisms through which diabetes-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) activation can affect male reproductive function; and (2) corroborate the interaction of previously established independent pathways. Male albino Wistar rats (14-weeks old) weighing 250-300 g received either a single intraperitoneal injection of streptozotocin (30 mg/kg or 60 mg/kg), represented as STZ30 or STZ60 respectively, or citrate buffer (control). Diabetes mellitus (DM) was confirmed if plasma glucose levels were ≥ 14 mmol/L after 1 week. Animals were sacrificed after 8 weeks of treatment by an overdose of sodium pentobarbital (160 mg/kg body weight). The testes and epididymides were harvested. The testes were used for biochemical and Western blot analysis, while sperm was retrieved from the epididymis and analysed with computer-aided sperm analysis. The blood glucose levels of STZ60 animals were above the cut-off point and hence these animals were regarded as diabetic. Diabetic animals presented with a non-significant increase in AGE and RAGE expression. Diabetic animals showed a significant increase in the expression of cleaved caspase 3 compared to control (p < 0.001), and these animals also presented with an increase in the expression of JNK (p < 0.05), PARP (p = 0.059) and p38 MAPK (p = 0.1). Diabetic animals also displayed decreased catalase activity accompanied by a non-significant increase in malondialdehyde levels. Additionally, there was a significant decrease in the percentage of progressively motile spermatozoa (p < 0.05) in diabetic animals. This study has shed some light on the interplay between DM, AGE, RAGE and mitogen-activated protein kinase signalling in the testes of diabetic rats, which can result in altered sperm function and contribute to male infertility. However, more studies are needed to better understand this complicated process.

Keywords: Advanced glycation end products; Apoptosis; Diabetes mellitus; Mitogen-activated protein kinases; Receptor for advanced glycation end products and sperm.